key: cord-0692979-62ttl5e3
authors: Barnabas, Ruanne V.; Wald, Anna
title: A Public Health COVID-19 Vaccination Strategy to Maximize the Health Gains for Every Single Vaccine Dose
date: 2021-01-05
journal: Ann Intern Med
DOI: 10.7326/m20-8060
sha: f484d3d16b0054f7f9393a60424b2e2b1d7bfe14
doc_id: 692979
cord_uid: 62ttl5e3

This commentary discusses the pros and cons of single-dose COVID-19 vaccination versus the 2-dose strategy.

pandemic, the basic reproductive number R 0 (the number of secondary infections in an entirely susceptible population) was between 2.5 and 3.5 (3) . Currently, the effective reproductive number R t (the number of secondary infections with infectious and susceptible individuals in the population) for SARS-CoV-2 hovers around 1 in most communities due to transmission mitigation strategies. Thus, even lack of complete protection on an individual level is likely to lower it sufficiently to achieve the R t less than 1 required to stop epidemic growth. With heterogeneities in mixing within the population such that similar people mix with each other rather than at random and with physical distancing, mask use, and mobility restrictions, the proportion requiring vaccination to reach herd immunity is likely to be lower than originally estimated (4) . Given the uneven spread of the infection, and the high potential for super-spreading events, providing partial protection to many is likely to be more effective than providing complete protection of a smaller subset of the population. A single-dose SARS-CoV-2 vaccine approach deals directly with the shortage of vaccines by vaccinating twice the number of people while maximizing the probability of achieving herd immunity.

Second, providing effective protection for as many people as soon as possible is more ethical because it distributes the scarce commodity more justly. A single-dose COVID-19 vaccination approach would follow the Advisory Committee on Immunization Practices' (ACIP) ethical principles for allocating initial supplies of the COVID-19 vaccine to 1) maximize benefits and minimize harms, 2) promote justice, 3) mitigate health inequities, and 4) promote transparency (5) . With administering only a single dose SARS-CoV-2 vaccine initially, twice the number of people could receive the vaccine and reduce harm from COVID-19. With limited vaccine supply, this could avoid potential exacerbation of health disparities and the creation of new ones.

Third, a single-dose vaccine approach could mitigate the higher incidence of many vaccine-associated adverse events seen with the second vaccine dose, increasing tolerability and thus likely acceptability in the general population. Reports from both vaccines have higher rates of systemic adverse events within 7 days after the second dose compared with the first dose (1, 2) . Fever, fatigue, headaches, chills, myalgias, or arthralgias were reported, with some participants taking a day off from work to recover.

Lastly, concern about behavioral disinhibition after immunization, such as abandoning masks and distancing, has been voiced. In fact, our own medical colleagues have voiced the hope that they will no longer need to See also:

This article was published at Annals.org on 5 January 2021.

Annals of Internal Medicine © 2021 American College of Physicians 1

wear personal protective equipment after receipt of such an effective vaccine. Thus, a vaccine that is only partly protective may ensure continued adherence to other mitigation strategies that will continue to be critical for many months to come. There is precedent for reduced-dose vaccine strategies to save lives during epidemics. In 2016, during a yellow fever outbreak in Kinshasa, Democratic Republic of the Congo, the global supply of yellow fever vaccines was insufficient to provide full-dose vaccination to millions of people. To mitigate the shortage, a fractional-dosing strategy was used to maximize the number of people receiving the yellow fever vaccination (6) . Since then, the results of fractional-dosing trials for yellow fever have been encouraging and the fractional-dosing approach has demonstrated protective, durable vaccine responses.

We acknowledge that detailed data on the efficacy of a single-dose vaccine are not available, including the very important question on protection from severe disease; data on effect on transmission are not available for any dose. The FDA has issued an emergency use authorization with an indication for a 2-dose vaccine, reflecting the design of the pivotal clinical trials. We agree that the 2-dose regimen in the initial clinical trials was preferable as the possibility for protection after immunization had to be demonstrated. However, public health bodies have flexibility in their authority to recommend and implement a vaccination program that does not stringently reflect the product label. Further, evaluation of a delayed, second-dose approach in high incidence settings would contribute data on the effectiveness of single-dose vaccination. Use of a single dose of the Pfizer-BioNTech and Moderna COVID-19 vaccines should be considered. 

C4591001 Clinical Trial Group. Safety and efficacy of the BNT162b2 mRNA covid-19 vaccine

FDA Briefing Document: Moderna COVID-19 Vaccine. 2020. Accessed at www.fda.gov/media /144434/download on 22

Challenges in creating herd immunity to SARS-CoV-2 infection by mass vaccination

A mathematical model reveals the influence of population heterogeneity on herd immunity to SARS-CoV-2

The advisory committee on immunization practices' ethical principles for allocating initial supplies of COVID-19 vaccine -United States

Fractional-dose yellow fever vaccination -advancing the evidence base

Pros and Cons of Two-Dose Versus Single-Dose Vaccination Strategy Current Author Addresses: Dr. Barnabas: University of Washington

Drafting of the article: R.V. Barnabas, A. Wald. Critical revision for important intellectual content